6511 Human epidermal growth factor receptor 2 (HER2) in gastric cancer (GC): results of the ToGA trial screening programme and recommendations for HER2 testing

Chung, Heesun; Bang, Yung‐Jue; Xu, Jingyu; Lordick, Florian; Sawaki, Akira; Липатов, О. Н.; Lehle, Michaela; Pickl, Marlene; Rueschoff, Josef; Cutsem, E. Van

doi:10.1016/s1359-6349(09)71233-9

Cited by 15 publications

(18 citation statements)

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“…Curiously, the the difference in the results between the study of Terashima et al and our study is unknown. The HER2 positivity rate in our study (15.7 %) was similar not only to that in the Western ToGA study (16.6 %), but also to that in a recent Japanese cohort study (15.5 %) [14,15]. Some studies have evaluated the prognostic impact of HER2 expression also in unresectable or recurrent gastric cancer.…”

Section: Discussionsupporting

confidence: 89%

Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer

et al. 2014

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Background Although some small-scale studies have suggested that human epidermal growth factor receptor 2 (HER2)-positive status in gastric cancer is associated with poor outcomes, the prognostic value of HER2 is still controversial. Since intratumoral HER2 heterogeneity is also an important issue, a multicenter large-scale study was conducted to evaluate the prognostic impacts of HER2 expression and intratumoral heterogeneity in gastric cancer. Methods This study included 1,148 gastric cancer patients who underwent gastrectomy in 11 institutions. HER2 expression was centrally evaluated with immunohistochemistry and fluorescence in situ hybridization, and intratumoral HER2 heterogeneity was evaluated for HER2-positive tumors. Overall survival was compared between HER2-positive and HER2-negative patients and between the homogeneous and heterogeneous groups. Results The HER2-positive rate was 15.7 %, and HER2 expression was significantly associated with histological type. HER2 expression scores obtained by immunohistochemistry showed a distinct influence on survival, and HER2-positive patients showed much poorer survival than HER2-negative patients [hazard ratio (HR) 1.59, 95 % confidence interval (CI) 1.24-2.02; P \ 0.001). The subgroup analysis by pathological tumor stage showed a similar trend of poor survival in HER2-positive patients. Both intestinal type and diffuse type showed significant poor survival in HER2-positive patients. Cox multivariate analysis revealed that HER2 expression was an independent prognostic factor (HR 1.96, 95 % CI 1.51-2.55; P \ 0.001). HER2 heterogeneity was observed in 75.4 % of HER2-positive cases, but the prognosis in the heterogeneous group was similar to that in the homogeneous group. Conclusions Our study demonstrated that HER2 overexpression is an independent prognostic factor in patients with any stage of resectable gastric cancer. Intratumoral HER2 heterogeneity did not affect prognosis.

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Section: Discussionsupporting

confidence: 89%

Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer

et al. 2014

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“…The guideline by the Japanese society of pathology as well as European society for medical oncology (ESMO) recommends IHC for the initial screening and FISH for IHC 2 + patients [29,30] while concurrent IHC and FISH test irrespective of IHC results is still common among National Cancer Institute (NCI)-designated cancer center [31]. Serum HER2 testing is less invasive, relatively inexpensive and quick manner, and our study demonstrated the potential of serum HER2 to detect false-negative results of tissue HER2 status.…”

Section: Discussionmentioning

confidence: 99%

Serum HER2 as an adjunct to assess HER2 status for advanced gastric cancer: A prospective multicenter trial (SHERLOCK)

et al. 2016

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Background: Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity of gastric cancer can be an obstacle to accurate HER2 assessment. Serum HER2, concentrations of the HER2 extracellular domain shed into the bloodstream, has a potential to compensate HER2 immunohistochemistry (IHC) but has not been scrutinized in gastric cancer. This study sought to explore the clinical utility of serum HER2 in gastric cancer. Methods: We performed a prospective multicenter trial (SHERLOCK trial) involving patients with allstage gastric or gastro-esophageal junction cancer. Serum HER2 was measured using direct chemiluminescence while tissue HER2 status was determined using IHC and fluorescent in situ hybridization. For stage IV cases, concordance between local and central laboratories in tissue HER2 assessment was also evaluated. Results: Of 224 patients enrolled, both tissue HER2 status and serum HER2 levels were successfully determined in 212 patients and 21% (45/212) were tissue HER2-positive. Serum HER2 levels, ranged from 4.5 to 148.0 ng/ml (median 10.3), correlated with tissue HER2 status (p ¼ 0.003). At a cut-off level of 28.0 ng/ml determined by receiver operating characteristics analysis, sensitivity, specificity, positive and negative predictive values of serum HER2 were 22.6%, 100%, 100% and 82.3%, respectively. All nine cases with elevated serum HER2 were tissue HER2-positive stage IV cases. Among 61 stage IV cases, the agreement rate for IHC scoring between the local and the central laboratories was 82% and tissue HER2 judgment was conflicting in five (8.2%) cases. Of these five cases, four were confirmed as false-negative and two of these four patients demonstrated elevated serum HER2. Conclusions: Serum HER2 levels correlated with tissue HER2 status in gastric cancer. Although the low sensitivity is a drawback, serum HER2 might be a useful adjunct tool to detect tissue HER2 false-negative gastric cancer.

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“…Amplification of HER-2 has been seen in 15%-19% of esophageal adenocarcinomas [15,64]. Although results for EGFR and histopathological response/ survival prediction with chemoradiotherapy have generally been positive [50,51], the method of assay of EGFR (immunohistochemistry [IHC], mutation) may determine the predictive impact, and optimal methods of assessment in this predictive context are yet to be resolved.…”

Section: Egfr Familymentioning

confidence: 99%

“…Similarly, although K-ras has clinical utility as a predictive biomarker for EGFR-targeted agents in colorectal adenocarcinomas and NSCLC, K-ras is wild type in 70%-80% of gastroesophageal cancer patients (much higher than in NSCLC and colorectal cancer patients), so its impact and use as a biomarker may be limited in gastroesophageal cancer. Updated results of a preplanned subgroup analysis of the Trastuzumab in Gastric Cancer (ToGA) trial (a phase III randomized trial of cisplatin and 5-fluorouracil or capecitabine with or without trastuzumab in advanced gastric and GEJ adenocarcinomas) have suggested that HER-2 IHC (score 3ϩ) with the use of HER-2 fluorescence in situ hybridization in borderline IHC (score 2ϩ) cases predicts those patients who will benefit from the addition of trastuzumab [15], and these data are potentially transferable to predictive biomarker use in the neoadjuvant setting. Trastuzumab is being assessed in the neoadjuvant setting; however, results may have to be readdressed in light of the HER-2 predictive biomarker data from the ToGA trial [15].…”

Section: Egfr Familymentioning

confidence: 99%

Predicting Response to Treatment in Gastroesophageal Junction Adenocarcinomas: Combining Clinical, Imaging, and Molecular Biomarkers

Bain

Petty

2010

The Oncologist

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After completing this course, the reader will be able to:1. Contrast the subtypes of gastroesophageal adenocarcinoma in order to select optimal therapeutic approaches for given subtypes.2. Compare the various tools (CT, MRI, PET, PET-CT, etc.) for evaluating response to therapy in order to determine whether to initiate new therapy.3. Evaluate response to neoadjuvant therapy, utilizing imaging, histopathogy of resected specimens, and biomarkers, to plan postoperative treatment.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTThe incidence of adenocarcinomas of the gastroesophageal junction (GEJ) is rapidly rising, and even in earlystage locoregional confined disease the 5-year survival rate rarely exceeds 25%-35%. Randomized trials and meta-analyses have demonstrated a benefit with neoadjuvant or perioperative chemotherapy and with neoadjuvant chemoradiotherapy. However, the optimal approach in individual patients is not clear and remains controversial. A consistent finding is that patients who have a histopathological response to neoadjuvant therapy are more likely to receive a survival benefit. These clinical data provide a strong argument for the urgent development of methods to predict histopathological response to neoadjuvant therapies for GEJ adeno- The Oncologist CME Program is located online at http://cme.theoncologist.com/.To take the CME activity related to this article, you must be a registered user. Gastrointestinal CancerThe

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6511 Human epidermal growth factor receptor 2 (HER2) in gastric cancer (GC): results of the ToGA trial screening programme and recommendations for HER2 testing

Cited by 15 publications

References 0 publications

Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer

Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer

Serum HER2 as an adjunct to assess HER2 status for advanced gastric cancer: A prospective multicenter trial (SHERLOCK)

Predicting Response to Treatment in Gastroesophageal Junction Adenocarcinomas: Combining Clinical, Imaging, and Molecular Biomarkers

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